ArticleThe American journal of pathology2009
The methylation of the TSC2 promoter underlies the abnormal growth of TSC2 angiomyolipoma-derived smooth muscle cells.
Article in The American journal of pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- GSK-J4 Suppresses Tumorigenesis by Targeting the PERK-c-Myc Pathway Through Endoplasmic Reticulum Stress Activation in Tuberous Sclerosis Complex.International journal of molecular sciences · 2026Article
- Epigenetic Insights into Tuberous Sclerosis Complex, Von Hippel-Lindau Syndrome, and Ataxia-Telangiectasia.Epigenomes · 2025Review
- Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy.Molecular biomedicine · 2022Review
- Distinct DNA Methylation Patterns of Subependymal Giant Cell Astrocytomas in Tuberous Sclerosis Complex.Cellular and molecular neurobiology · 2022Article
- Primary TSC2International journal of molecular sciences · 2022Article
- Article
- Recent advances in human stem cell-based modeling of Tuberous Sclerosis Complex.Molecular autism · 2020Review
- Tuberous sclerosis complex: new insights into clinical and therapeutic approach.Journal of nephrology · 2019Review
- The Lymphangioleiomyomatosis Lung Cell and Its Human Cell Models.American journal of respiratory cell and molecular biology · 2018Review
- Human renal angiomyolipoma cells of male and female origin can migrate and are influenced by microenvironmental factors.PloS one · 2018Article
- The genomic landscape of tuberous sclerosis complex.Nature communications · 2017Article
- Inhibition of class I histone deacetylases blunts cardiac hypertrophy through TSC2-dependent mTOR repression.Science signaling · 2016Article
- Che-1-induced inhibition of mTOR pathway enables stress-induced autophagy.The EMBO journal · 2015Article
- Article
- Anti-EGFR antibody reduces lung nodules by inhibition of EGFR-pathway in a model of lymphangioleiomyomatosis.BioMed research international · 2015Article
- TSC2 epigenetic defect in primary LAM cells. Evidence of an anchorage-independent survival.Journal of cellular and molecular medicine · 2014Article
- PTEN hamartoma of soft tissue: a distinctive lesion in PTEN syndromes.The American journal of surgical pathology · 2012Article
- Article
- Phenotypic characterization of disseminated cells with TSC2 loss of heterozygosity in patients with lymphangioleiomyomatosis.American journal of respiratory and critical care medicine · 2010Article
- Lymphangioleiomyomatosis and TSC2-/- cells.Lymphatic research and biology · 2010Review
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Authors and funding
9 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tuberous sclerosis complex (TSC) is an autosomal-dominant disease that is caused by mutations in either the TSC1 or TSC2 gene. Smooth muscle-like cells (ASMs) were isolated from an angiomyolipoma of a patient with TSC. These cells lacked tuberin, were labeled by both HMB45 and CD44v6 antibodies, and had constitutive S6 phosphorylation. The cells bear a germline TSC2 intron 8-exon 9 junction mutation, but DNA analysis and polymerase chain reaction amplification failed to demonstrate loss of heterozygosity. Testing for an epigenetic alteration, we detected methylation of the TSC2 promoter. Its biological relevance was confirmed by tuberin expression and a reduction in HMB45 labeling and S6 constitutive phosphorylation after exposure to the chromatin-remodeling agents, trichostatin A and 5-azacytidine. These cells were named TSC2(-/meth) ASMs. Their proliferation required epidermal growth factor in the medium as previously described for TSC2(-/-) ASMs. Blockade of epidermal growth factor with monoclonal antibodies caused the death of TSC2(-/meth) ASMs. In addition, rapamycin effectively blocked the proliferation of these cells. Our data show for the first time that methylation of the TSC2 promoter might cause a complete loss of tuberin in TSC2 cells, and that the pathogenesis of angiomyolipomas might also originate from epigenetic defects in smooth muscle cells. Additionally, the effect of chromatin-remodeling agents in these cells suggests a further avenue for the treatment of TSC as well as lymphangioleiomyomatosis.
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